Role of Ca-NFAT Signaling Pathway in Ph ALL Drug-resistance Mediated by Bone Marrow Stromal Cells.
10.19746/j.cnki.issn.1009-2137.2019.03.012
- Author:
Huan-Xin ZHANG
1
;
Ya-Hui HAN
2
;
Ting-Ting QIU
2
;
Yao YAO
2
;
Sheng-Yun ZHU
2
;
Ming-Shan NIU
2
;
Ling-Yu ZENG
2
;
Zhen-Yu LI
2
;
Zhi-Ling YAN
3
,
4
;
Kai-Lin XU
4
,
5
Author Information
1. The First Clinical Medical College, Nanjing Medical University，Nanjing 210029, Jiangsu Province, China,Department of Hematology; The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, Jiangsu Province, China.
2. Department of Hematology; The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, Jiangsu Province, China.
3. Department of Hematology; The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, Jiangsu Province, China,E-mail: hematology_md@
4. com.
5. The First Clinical Medical College, Nanjing Medical University，Nanjing 210029, Jiangsu Province, China,Department of Hematology; The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, Jiangsu Province, China,E-mail:lihmd@
- Publication Type:Journal Article
- MeSH:
Bone Marrow Cells;
Cell Line, Tumor;
Humans;
Imatinib Mesylate;
Mesenchymal Stem Cells;
NFATC Transcription Factors;
Precursor Cell Lymphoblastic Leukemia-Lymphoma;
Signal Transduction
- From:
Journal of Experimental Hematology
2019;27(3):717-722
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the role of Ca-NFAT signaling pathway in Ph-ALL drug resistance mediated by bone marrow stromal cells.
METHODS:The transcription level of NFAT mRNA in Sup-B15 cells and Ph ALL primary cells was detected by polymerase chain reaction. The expression of P-glycoprotein in Sup-B15 cells was detected by flow cytometry. The change of NFAT protein in Sup-B15 cells was detected by Western blot. AnnexinV/7-AAD was used to label cells. Flow cytometry was used to detect cell apoptosis; Fluo 3-AM dye was used to label cells, and flow cytometry used to detect changes of Ca concentration in leukemia cells.
RESULTS:NFAT expression could be detected in both Sup-B15 and Ph ALL primary cells; P-glycoprotein could not be detected by flow cytometry; CAS could significantly inhibit NFAT protein expression in clinically applied drug concentrations (2.5, 5 μmol/L); Clinically applied concentration of CAS (2.5, 5 μmol / L) has no significant effect on the apoptosis of Sup-B15 cells, while higher concentration of CAS (10 μmol / L) could induce apoptosis of Sup-B15 cells. Bone marrow stromal cells OP9 could, decrease the sensitivity of Sup-B15 cells and Ph ALL primary cells to imatinib (IM); After co-culture with bone were marrow stromal cells, the Ca concentration in Sup-B15 cells was enhanced, the levels of NFAT protein and nullear protein in sup-B15 cells also were enhanced. The addition of CAS in co-culture system could inlibit the Ca-NFAT signaling pathway, reduce the protective effect of OP9 on Sup-B15 cells.Conclution:The Ca-NFAT sigualing pathway, contributes to the survival of Ph ALL cells. Bone marrow stromal cells can mediate the resistance of Ph ALL cells to IM by activating Ca-NFAT signaling pathway.
